Network Modulation in Alzheimer's Disease

NCT04045990 | Completed FDA Device

• 1 other identifier: 2018P001362
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the effects of non-invasive brain stimulation on memory and language ability in patients with two phenotypic variations of underlying Alzheimer disease pathology: amnestic mild cognitive impairment (aMCI) and logopenic variant of primary progressive aphasia (lvPPA). This study will use repetitive Transcranial Magnetic Stimulation (rTMS) to stimulate nodes of networks that are thought to be affected in these two conditions. Specifically, a node of the Default Mode Network (DMN)-the angular gyrus (AG)-will be stimulated in aMCI patients; and a node of the language network-the posterior inferior frontal gyrus (pIFG) will be stimulated in patients with lvPPA. We will use functional connectivity MRI (fcMRI) to assess changes in functional network architecture following the stimulation. We will also assess putative cognitive improvements resulting from the stimulation by in-depth language testing in lvPPA patients and in-depth memory testing in aMCI patients.

Conditions

Alzheimer Disease; Primary Progressive Aphasia; Mild Cognitive Impairment

Outcome Measures

Primary Outcomes (9)

• Boston Naming Test

  A test of confrontation naming of drawn pictures.

  Up to 5 weeks

• Western Aphasia Battery-repetition

  A test of the ability to repeat phonetically complex phrases

  Up to 5 weeks

• Western Aphasia Battery-reading comprehension

  A test of the ability to correctly comprehend read material

  Up to 5 weeks

• Western Aphasia Battery-spelling

  A test of the ability to spell irregular words.

  Up to 5 weeks

• Controlled Oral Word Association Test

  A test of word generation, e.g. generation of as many words as possible beginning with a certain letter of the alphabet.

  Up to 5 weeks

• Cambridge Semantic Battery

  A test of semantic knowledge through word-pairings.

  Up to 5 weeks

• The Northwestern Anagram Test

  A test of non-verbal production of sentences.

  Up to 5 weeks

• Picture Description Test

  A test in which patients write a paragraph describing a picture, such as a picnic or the cookie theft picture.

  Up to 5 weeks

• Changes in intrinsic functional connectivity

  Changes in region-to-region functional connectivity within the stimulated networks will be assessed, e.g. changes in connectivity in the DMN will be assessed in aMCI patients and changes in the language network will be assessed in lvPPA patients.

  Up to 5 weeks

Study Arms (2)

Active stimulation

EXPERIMENTAL

Active rTMS will be administered with a MagPro X100 stimulator (MagVenture, Denmark), using a 70 mm figure-of-eight liquid cooled coil capable of doing active or sham stimulation (e.g. the Cool B70 coil or the Cool B65 A/P coil). Active rTMS will be delivered at 80-120% of a patient's resting or active motor threshold. rTMS will be administered in an excitatory pattern as 20Hz. Stimulation parameters will remain well within established safety guidelines (Rossi et al. 2009).

Device: repetitive transcranial magnetic stimulation (rTMS)

SHAM stimulation

SHAM COMPARATOR

SHAM stimulation will also be administered with a MagPro X100 stimulator (MagVenture, Denmark), using a 70 mm figure-of-eight liquid cooled coil capable of doing active or sham stimulation (e.g. the Cool B70 coil or the Cool B65 A/P coil). SHAM rTMS will be delivered at 80-120% of a patient's resting or active motor threshold. SHAM stimulation will be delivered to the exact same cortical targets as active rTMS. While no electromagnetic stimulation will be delivered during SHAM, the sounds will approximate active stimulation and skin electrodes will approximate the sensation of active rTMS. Inclusion of a sham condition in this protocol is critical to measure whether or not the stimulation is improving memory or language performance, or whether practice effects or other non-specific effects are responsible for any changes in memory or language performance which may be observed.

Device: repetitive transcranial magnetic stimulation (rTMS)

Interventions

repetitive transcranial magnetic stimulation (rTMS) DEVICE

rTMS is a method to focally and reversibly stimulate a pre-specified cortical target. rTMS works through the principle of electromagnetic induction.

Active stimulation; SHAM stimulation

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients, age 18-90, who carry a diagnosis of either the logopenic variant (lvPPA) of PPA or amnestic MCI (aMCI). Patients must have been observed for at least one year by a specialized clinician.
• The presence of underlying AD pathology must be verified by a prior amyloid-PET and/or Tau-PET imaging (done as part of a prior protocol), or CSF biomarkers of AD pathology.
• Patients with lvPPA must have at least mild to moderate language impairment.
• Patients with aMCI must meet criteria for this condition, including the presence of at least mild to moderate episodic memory impairment.
• Patients must be native English speakers.
• Patients must have a study partner (e.g. spouse, sibling, adult child, friend) who can accompany them to all study visits.

You may not qualify if:

• Any history of seizures, unexplained loss of consciousness or a first-degree family member with epilepsy (to ensure safety to receive rTMS).
• Any history of significant co-occurring neurological illness unrelated to the neurodegenerative disease in question (e.g. multiple sclerosis), or significant medical problems (e.g. poorly controlled diabetes/hypertension or cancer within 5 years).
• Active symptoms of major depressive disorder, bipolar disorder, schizophrenia, substance use disorder or significant premorbid intellectual disability according to DSM criteria.
• MRI evidence of significant (e.g. confluent leukoariosis or stroke) cerebrovascular disease, hydrocephalus or the presence of a space-occupying intra-cranial mass.
• Contraindications to MRI or rTMS including: cardiac pacemaker or pacemaker wires, neurostimulators, implanted pumps, metal in the body (rods, plates, screws, shrapnel, dentures, IUD), surgical aneurysm clips in the head, previous neurosurgery or cochlear implants.
• In line with published MGH IRB guidelines for rTMS, pregnancy must be ruled out by urine ß-HCG if answers to screening questions suggest that pregnancy is possible and if female participants are premenopausal and of child-bearing age. Subjects will not be able to enroll if they are breastfeeding.

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Charlestown, Massachusetts, 02129, United States

Location

MeSH Terms

Conditions

Alzheimer Disease; Aphasia, Primary Progressive; Cognitive Dysfunction

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Aphasia; Speech Disorders; Language Disorders; Communication Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Cognition Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: All participants will undergo SHAM stimulation as a control condition. They will be blinded as to whether they are receiving active or SHAM stimulation.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Neurology

Model Details: Patients with each condition will each undergo, in a crossover, within-subject design, two clocks of rTMS: active and SHAM.The order of active and SHAM blocks will be counterbalanced across subjects.

Study Record Dates

• First Submitted: August 29, 2018
• First Posted: August 6, 2019
• Study Start: September 1, 2018
• Primary Completion: January 31, 2022
• Study Completion: March 1, 2022
• Last Updated: March 17, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)